Adam Green's Hatchet II picks up at the exact moment that 2006's Hatchet ends, wherein the quiet but hot-tempered Marybeth (Danielle Harris) is in a small boat in the Louisiana swamps, screaming for her life as she tries to free herself from the clutches of the deformed, swamp-dwelling killer Victor Crowley (Kane Hodder). Crowley has murdered Marybeth's family and other fellow vacationers who had come together on a tourist excursion in the swamplands outside of New Orleans.

Marybeth escapes from Crowley and manages to make it back to civilization, where she once again encounters voodoo shop proprietor Reverend Zombie (Tony Todd), who had helped to arrange Marybeth and company's earlier, ill-fated tour of the area. To help Marybeth and also serve his own secret agenda, Reverend Zombie recruits a hardened pack of hunters to head back into the swamp to seek revenge on Victor Crowley.